Protective effect of arabic gum against cardiotoxicity induced by doxorubicin in mice: a possible mechanism of protection

Arabic gum (AG) is a naturally occurring compound that has been proposed to possess potent antioxidant activity. In this study, the possible effects whereby AG could protect against cardiotoxicity induced by doxorubicin (DOX) in mice were carried out. Administration of single dose of DOX (15 mg/kg, i.p.) induced cardiotoxicity 72 h, manifested biochemically by a significant elevation of serum creatine kinase (CK) (EC 2.7.3.2). In addition, cardiotoxicity was further confirmed by the significant increase in lipid peroxides measured as malondialdehyde (MDA). Administration of AG (25 g/kg) orally for 5 days before and 72 h after DOX injection produced a significant protection against cardiotoxicity induced by DOX. This was evidenced by significant reductions in serum CK and cardiac lipid peroxides. The effect of AG was examined on the superoxide anion radical generated by enzymatic and nonenzymatic methods. The results indicate that AG is a potent superoxide scavenger. The superoxide scavenging effect of AG may explain, at least in part, the protective effect of AG against cardiotoxicity induced by DOX.     

A benzoquinone and flavonoids from Cyperus alopecuroides

A benzoquinone, named alopecuquinone, was isolated from the ethanol extract of the inflorescences of Cyperus alopecuroides. Its structure was primarily elucidated by spectroscopic analysis including 1H, 13C NMR, APT, HMQC, 1H-1H COSY and CIMS. The known flavonoids, vicenin 2, orientin, diosmetin, quercetin 3,3'-dimethyl ether and its 3,4'-dimethyl ether, were also isolated and characterized. The ethanol extract of the plant material showed moderate estrogenic activity using a strain of Saccharomyces cerevisiae.     

Assessing potentiation of the (α4)3(β2)2 nicotinic acetylcholine receptor by the allosteric agonist CMPI

The extracellular domain of the nicotinic acetylcholine receptor isoforms formed by three α4 and two β2 subunits ((α4)3(β2)2 nAChR) harbors two high-affinity “canonical” acetylcholine (ACh)-binding sites located in the two α4:β2 intersubunit interfaces and a low-affinity “noncanonical” ACh-binding site located in the α4:α4 intersubunit interface. In this study, we used ACh, cytisine, and nicotine (which bind at both the α4:α4 and α4:β2 interfaces), TC-2559 (which binds at the α4:β2 but not at the α4:α4 interface), and 3-(2-chlorophenyl)-5-(5-methyl-1-(piperidin-4-yl)-1H-pyrrazol-4-yl)isoxazole (CMPI, which binds at the α4:α4 but not at the α4:β2 interface), to investigate the binding and gating properties of CMPI at the α4:α4 interface. We recorded whole-cell currents from Xenopus laevis oocytes expressing (α4)3(β2)2 nAChR in response to applications of these ligands, alone or in combination. The electrophysiological data were analyzed in the framework of a modified Monod–Wyman–Changeux allosteric activation model. We show that CMPI is a high-affinity, high-efficacy agonist at the α4:α4 binding site and that its weak direct activating effect is accounted for by its inability to productively interact with the α4:β2 sites. The data presented here enhance our understanding of the functional contributions of ligand binding at the α4:α4 subunit interface to (α4)3(β2)2 nAChR-channel gating. These findings support the potential use of α4:α4 specific ligands to increase the efficacy of the neurotransmitter ACh in conditions associated with decline in nAChRs activity in the brain.     

Deformation of nasal septal cartilage during mastication

The cartilaginous nasal septum plays a major role in structural integrity and growth of the face, but its internal location has made physiologic study difficult. By surgically implanting transducers in 10 miniature pigs (Sus scrofa), we recorded in vivo strains generated in the nasal septum during mastication and masseter stimulation. The goals were (1) to determine whether the cartilage should be considered as a vertical strut supporting the nasal cavity and preventing its collapse, or as a damper of stresses generated during mastication and (2) to shed light on the overall pattern of snout deformation during mastication. Strains were recorded simultaneously at the septo‐ethmoid junction and nasofrontal suture during mastication. A third location in the anterior part of the cartilage was added during masseter stimulation and manipulation. Contraction of jaw closing muscles during mastication was accompanied by anteroposterior compressive strains (around ?1,000 με) in the septo‐ethmoid junction. Both the orientation and the magnitude of the strain suggest that the septum does not act as a vertical strut but may act in absorbing loads generated during mastication. The results from masseter stimulation and manipulation further suggest that the masticatory strain pattern arises from a combination of dorsal bending and/or shearing and anteroposterior compression of the snout. J. Morphol., 2009. © 2009 Wiley‐Liss, Inc.     

Benzo[a]pyrene, 3-methylcholanthrene and beta-naphthoflavone induce oxidative stress in hepatoma hepa 1c1c7 Cells by an AHR-dependent pathway

Polycyclic aromatic hydrocarbons have been shown to cause oxidative stress in vitro and in vivo in various animal models but the mechanisms by which these compounds produce oxidative stress are unknown. In the current study we have investigated the role of the aryl hydrocarbon receptor (AHR) in the production of reactive oxygen species (ROS) by its cognate ligands and the consequent effect on cyp1a1 activity, mRNA and protein expressions. For this purpose, Hepa 1c1c7 cells wild-type (WT) and C12 mutant cells, which are AHR-deficient, were incubated with increasing concentrations of the AHR-ligands, benzo[a]pyrene (B[a]P, 0.25-25 μM), 3-methylcholanthrene (3MC, 0.1-10 μM) and β-naphthoflavone (βNF, 1-50 μM). The studied AHR-ligands dose-dependently increased lipid peroxidation in WT but not in C12 cells. However, only B[a]P and βNF, at the highest concentrations tested, significantly increased H₂O₂ production in WT but not C12 cells. The increase in lipid peroxidation and H₂O₂ production by AHR-ligands were accompanied by a decrease in the cyp1a1 catalytic activity but not mRNA or protein expressions, which were significantly induced in a dose-dependent manner by all AHR-ligands, suggesting a post-translational mechanism is involved in the decrease of cyp1a1 activity. The AHR-ligand-mediated decrease in cyp1a1 activity was reversed by the antioxidant N-acetylcysteine. Our results show that the AHR-ligands induce oxidative stress by an AHR-dependent pathway.     

Effect of aqueous extract from Nigella sativa L. on guinea pig isolated heart

A potent inhibitory effect of aqueous extract from N. sativa on calcium channel of guinea pig heart was found comparable and even greater than that of diltazem. The results may also indicate an opening effect for the plant on potassium channel of isolated heart.     

The application of databases and PCR in the cloning of glycosidase genes from the protozoan Tritrichomonas foetus

Conserved sequence amplification (CSA) has been used to obtain sequence data for two glycosidase genes from the primitive eukaryote Tritrichomonas foetus. Few genes have been cloned from this organism, and there is little information concerning protein sequence. CSA is reliant on the use of database searches to identify short sequences of 3–9 amino acids conserved within a protein across a wide range of species. PCR primers are then constructed based on this sequence data and the DNA is amplified and sequenced. In the case of the β-galactosidase gene, N-terminal amino acid sequence data were used to construct a primer that replaced the upstream primer to ensure the amplified product was related to β-d galactosidase CSA was also applied to the gene encoding the enzyme β-N-acetyl-d-glucosaminidase from T. foetus, but in this case a segment of DNA was amplified, which, if correct, should contain a third conserved motif. The products of the CSA were sequenced, and the data obtained were compared to data in the SwissProt database. The results obtained suggest that this approach is useful for the cloning of genes to obtain novel sequence data from organisms where little genetic information is available.     

Hereditary muscular dystrophy: bioengineering approaches to muscle fiber repair

Restoration of disturbed functions of the organs and tissues is the main task of contemporary genetic and cellular biotechnology, including genetic and cellular therapy. Duchenne dystrophy, one of the most widespread human genetic diseases, is at the same time the most extensively studied from the viewpoint of both genetic and histological changes leading to muscle fiber degeneration. Although many studies carried out on models, recognized analogous to Duchenne dystrophy, gave hopeful results, clinical tests with the use of developed methods gave no expected success and the rate of mortality from this disease amounts to 100%. Based on the world experience and analysis of the authors' data, possible influence of the intensity of regeneration on success of genetic and cellular therapy has been considered.     

Cellular imaging at 1.5 T: detecting cells in neuroinflammation using active labeling with superparamagnetic iron oxide

The ability to visualize cell infiltration in experimental auto-immune encephalomyelitis (EAE), a well-known animal model for multiple sclerosis in humans, was investigated using a clinical 1.5-T magnetic resonance imaging (MRI) scanner, a custom-built, high-strength gradient coil insert, a 3-D fast imaging employing steady-state acquisition (FIESTA) imaging sequence and a superparamagnetic iron oxide (SPIO) contrast agent. An "active labeling" approach was used with SPIO administered intravenously during inflammation in EAE. Our results show that small, discrete regions of signal void corresponding to iron accumulation in EAE brain can be detected using FIESTA at 1.5 T. This work provides early evidence that cellular abnormalities that are the basis of diseases can be probed using cellular MRI and supports our earlier work which indicates that tracking of iron-labeled cells will be possible using clinical MR scanners.